Monitoring IgE-mediated Food Allergies

• In general, the longer a food allergy persists (i.e. into the late teenage and early adult years) the less likely that the patient's food allergy will resolve

Food	Monitoring	Natural course
Cow's Milk	Annual sIgE Offer regular milk challenge when sIgE ≤2 When sIgE ≤2, ~50% chance of negative challenge; consider using lower cutoff in children <2 yo If sIgE falls 99% over >1 year, there is 94% chance of negative challenge Consider baked milk challenge when sIgE ≤10-35, with lower threshold for younger children (Wegrzyn) Majority (70-80%) of children with milk allergy tolerate baked foods containing milk (e.g. muffin and waffle made with milk) Low casein specific IgE level is a very favorable prognostic factor for tolerance of baked milk, with casein sIgE >20 unlikely to pass and <0.94 unlikely to fail a baked milk challenge; sIgE <~5 may be optimal decision point (~75% sens/spec) In one study, milk SPT <7 and <12 mm was 100% and 90% predictive of passing a baked milk challenge	Peaks during first year of life and remits during childhood, almost always outgrown Prospective studies Resolution in 51% within 2 years and 80% within 3-4 years of diagnosis. Resolution in 53% by median age of 5.25 yo Risk factors for persistence Referral population (vs. primary care) Multiple food allergy, other atopic diseases Higher peak sIgE or larger SPT wheal Sensitization to alpha-1 casein, beta-casein, and kappa-casein regardless of patient age Intolerance of foods containing heated/baked milk CoFAR cow's milk allergy resolution calculator - for patients <15 months old using their initial test SPT and sIgE test values
Hen's Egg	Annual sIgE Offer regular egg challenge when egg white sIgE ≤2 When sIgE ≤2, ~50% chance of negative challenge; consider using lower cutoff in children <2 yo HealthNuts study of 11-15 mo Australian infants: egg white SPT 4 mm or sIgE 1.7 with 95% PPV for positive raw egg challenge sIgE to ovomucoid >10.8 correlated with a high risk (95% specific) of reacting to boiled or raw egg white, whereas a level <1.2 correlated with a low risk of reaction (95% sensitive) to boiled egg white (even if the patient might react to raw) sIgE to ovomucoid >22.4 was 100% specific for positive OFC to boiled egg white; sIgE to ovomucoid ~7-8 with ~50% probability of positive OFC to boiled egg white In children who developed allergy <4 yo, if sIgE dropped 50, 75, 90, and 99% over 1 year, there was a 52, 65, 78, and 95% chance of negative challenge. Majority (70-80%) of children with egg allergy tolerate extensively heated egg (e.g. muffin and waffle made with eggs) Consider baked egg challenge when egg white sIgE <7-50, with lower threshold for younger children (Wegrzyn) Burks: consider baked egg challenge when ovomucoid sIgE ≤2 kU/L and SPT to egg white <8 mm In one study, negative predictive value was 89, 77, and 71% with egg white sIgE levels <2.5, 5, and 10 In one study, 100% passed if egg white SPT <10 mm, 78% if 10-19 mm, 80% if 20-29 mm, and 66% (2 of n=3) if >30 mm In a large retrospective study, 90% passed (NPV 90%) if ovomucoid sIgE <0.35, egg white sIgE <6, and egg white SPT <11 mm; ovomucoid sIgE >3.38, egg white >9.65, and egg white SPT >25 mm >95% specific in predicting positive challenges Egg white SPT <3 mm may identify candidates for home challenge (100% passed) HealthNuts study of 11-15 mo Australian infants: egg white SPT 9-10 mm with 50% PPV, 11 mm with 82% PPV, and sIgE 50 with 88% PPV for positive baked egg challenge	Usually resolves within several years of diagnosis (usually during childhood, majority (80%) by adulthood 50% with resolution by 6 yo; persistence associated with more severe index reaction and higher sIgE/SPT levels 4, 26, 48, and 68% with resolution at 4, 8, 12, and 16 yo sIgE >50 associated with persistence Tolerance is gained twice as rapidly to well-cooked egg than uncooked egg (median age resolution 5.6 years vs. 10.3) Resolution tends to occurs in stages starting with tolerance to well-cooked egg (e.g. cake), then lightly cooked egg (e.g. scrambled) followed finally by raw egg
	Mt. Sinai Egg Challenge Algorithm (2012)
Peanut	Annual sIgE Offer challenge when 4 yo, no reaction in past 1-2 years, and sIgE ≤2 (~60% chance of negative challenge) Low/undetectable sIgE level is best predictor of a negative challenge but 4-28% with negative sIgE have positive challenge If OFC negative, the patient should ingest a serving of peanut weekly In patients with persistent allergy or if sIgE remains unchanged for years, test less frequently Fleischer: I only challenge patients when sIgE <2 Burks: challenge if peanut sIgE ≤2 and SPT <8 mm HealthNuts study of 11-15 mo Australian infants: peanut SPT 2-3 mm or sIgE ~2.5 with 50% PPV and SPT 8 mm or sIgE 34 with 95% PPV for positive peanut challenge sIgE/tIgE ratio 0.42%/2.36% associated with OFC pass/fail in a group of children with peanut SPT <8 mm and sIgE <15 kU/L	Resolution rate often quoted as 20-25%; in one study 27% with resolution by 12 yo Spontaneous resolution of early-onset peanut allergy occurs predominantly before 6 yo and at a much lower frequency after 10 yo Recurrence of allergy after negative OFC may occur in up to 8% and may be associated with lack of regular intake (at least weekly to monthly) after a negative challenge
Tree nut	Annual sIgE Offer challenge when 4 yo, no reaction in past 1-2 years, and sIgE <5 (~60% chance of negative challenge) 58, 63, and 75% of children with negative challenge had sIgE levels <5, <2, and negative sIgE/tIgE ratio 0.29%/1.9% associated with OFC pass/fail in a group of children with tree nut SPT <8 mm and sIgE <15 kU/L Low/undetectable sIgE level is best predictor of a negative challenge but up to 10% with negative sIgE/SPT have positive challenge If negative, the patient should ingest a serving of culprit tree nut weekly In patients with persistent allergy or if sIgE remains unchanged for years, test less frequently	~10% with resolution over time Resolution less likely if reactions to >2 different tree nuts If peanut allergy resolved, more likely to outgrow tree nut allergy. However, resolution of peanut does not mean resolution of tree nuts or seeds.
Sesame	Annual sIgE Challenge to sesame if sIgE ≤20, avoidance if >20. If SPT negative, sesame may be introduced into the diet. (Sampson) HealthNuts study of 11-15 mo Australian infants: sesame SPT 2-3 mm or sIgE 10 with 50% PPV, SPT 8 mm with 95% PPV, and sIgE 50 with 86% PPV for positive sesame challenge	20-30% with resolution over time
Wheat	Annual sIgE Consider oral challenge to wheat at least every 2 years regardless of sIgE level Based on observation that resolution is likely to occur in a two-year time span in a younger child (though resolution may occur when older) sIgE <20 to <100 have been associated with 50% negative challenge rate depending on study/population. In one survey, 60% with sIgE level <20 kU/L with negative challenge and 50% with <50 kU/L with negative challenge Median sIgE levels associated with resolution 21-25; persistent allergy 62-70 (in 2-8 yo).	Usually outgrown by adolescence In general population, 80% resolved by 5 yo In referral population, 29, 56, and 70% with negative challenge at 4, 8, and 14 yo
Soy	Annual sIgE Offer challenge to soy when IgE level is low, however this is not well defined Soy sIgE and SPT may be artificially elevated in patients with peanut allergy, which makes these tests even more difficult to interpret	In referral population, 25, 45, and 69% with negative challenge by age 4, 6, and 10 years Generally outgrown more quickly than egg or milk allergy
Seafood	Annual sIgE Patients who react to fresh tuna and salmon usually tolerate canned versions of these fish. If interested in eating the canned form, additional testing and OFC are suggested.	Considered to be persistent in most cases In a US survey, allergy developed in adulthood for 40-60% and 3-4% reported developing tolerance over time
Other foods	In general, annual sIgE, with increasing interval if level is unchanging

Above mostly adapted from Robert Wood
sIgE = serum specific IgE to food via Phadia (Thermo Fisher Scientific) ImmunoCAP

Food Allergy Prevalence

Oral Food Challenge sIgE Cut-offs

~50% Negative Oral Food Challenge
Test	sIgE (ImmunoCap)	----SPT----
----Cow’s milk----	≤2	n/a
Egg	≤2	≤3
Peanut	≤2 with and ≤5 without history of reaction	≤3

~95% Positive OFC
Test	-----sIgE (ImmunoCap)-----	-----SPT-----
-----Cow’s milk-----	≥15 (≥5 if <1 yo)	≥8
Egg	≥7 (≥2 if <2 yo)	≥7
Peanut	≥14	≥8
Fish	≥20
Walnut	≥18.5
~73-74% Positive OFC
Soy	≥30
Wheat	≥26

Oral Food Challenge Procedure

References